Article
The synergistic antitumoral effect of TRAIL and Taurolidin on human fibrosarcoma in athymic nude mice
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Published: | May 20, 2011 |
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Introduction: Soft tissue sarcoma represents a rare entity, causing significant morbidity due to local recurrence and limited treatment options. The effectiveness of established chemotherapeutics is disappointing so far. Therefore, combinations of TRAIL and Taurolidine which showed promising results inducing apoptosis in vitro. In the present study, we investigated a combinatorial approach using TRAIL and Taurolidine in an athymic mice model to evaluate the effects in vivo.
Materials and methods: The antitumor effect of TRAIL and Taurolidin in mice (n=40) with xenografted fibrosarcoma ( HT1080, 1x 106 cells/subcutaneously/backside) was examined by intraperitoneal injection. Therefore every 10 mice were treated with 2, 10 and 20 µl TRAIL 1500 µl Taurolidin 2% and 1500µl PBS (control) for 4 days. After a break of 2 days, the animals were treated with half dose of Taurolidin/PBS for 4 days. The sizes of the tumors and mice’s weights were determined. The xenograft tumors and organs (lung, kidney, liver, heart, skin) were explanted examined histologically.
Results: In the TRAIL and Taurolidin injected group, reduction of tumor size showed a significant difference compared to mice in the control group (2µl TRAIL Taurolidin 2% vs. control p=0,001; 10µl TRAIL Taurolidin 2% vs. control p=0,008 and 20µl TRAIL Taurolidin 2% p=0,01).
In the 2µl group 6, in the 10µl group 8 and in the 20µl group 7 mice died within the 14 day period. In the control group all animals survived the treatment period.Histological analysis of the organs found no relevant impairments, but a moderate peritoneal serositis.
Conclusion: Our findings demonstrate that TRAIL and Taurolidin inhibited growth of xenografted tumors HT1080 in nude mice, suggesting that these substances may be a new therapeutic option. However, a high mortality was observed in the treatment groups in the absence of organic correlate. Therefore more examinations concerning the effect of Taurolidin and TRAIL and a revision of the animal model are necessary.